The overall scientific goal of the Cancer Immunotherapeutics Program (CIP) is to develop immunologic based therapeutics for the treatment of both hematologic malignancies and solid tumors. The program is an outgrowth of two major research efforts at COH, Radioimmunotherapy and Hematopoietic Transplantation for Hematologic Malignancies. The focus of the program is to utilize the advances in molecular immunology to combat a variety of malignancies. The Program has three major subdivisions: Radioimmunotherapy (RIT), Cellular Immunotherapy(CIT), and Molecular Immunotherapeutics(MIT). The specific aims are: (a) to develop genetically engineered antibody constructs as diagnostic imaging agents directed against CEA, Her2, and PSCA (prostate stem cell antigen); (b) to apply genetically engineered radiolabeled antibody constructs for the treatment of patients with solid malignancies; (c) to develop radiolabeled anti-lymphoma/leukemia antibodies as conditioning reagents for stem cell transplantation; (d) to explore adoptive T-cell therapy for targeting minimal residual disease following stem cell transplantation, targeting metastatic solid tumors, and targeting primary brain tumors; (e) to develop immunofusions between antibodies and lymphokines as cancer therapeutics used alone or with RIT or CIT); (f) to develop dendritic cell immunotherapy based on AAV carrying target peptide epitopes for CML and human papilloma virus. The elements of this program are highly interactive with each other and highly interactive with other programs within the Cancer Center. The Clinical and Experimental Therapeutics Program collaborates on the RIT trials combining chemotherapy. The Hematologic Malignancies Program collaborates on the clinical aspects of the RIT/stem cell transplantation protocols as well as the clinical aspects of the adoptive T-cell protocols for patients with hematologic malignancies. In addition, the program has collaborated extensively outside COH with UCLA, MSKCC, and FHCRC. The Program is led by Dr. Andrew Raubitschek and Dr. Michael Jensen. Their combined experience in the molecular engineering of antibodies, the molecular engineering of T cells, the production and purification of clinical grade antibodies and cellular therapeutics, and their ability to radiolabel the products to evaluate localization in patients and animals provide the required infrastructure to build an effective translational research program in Cancer Immunotherapeutics. This clinical effort is significantly aided by the recently completed Center for BioMedicine and Genetics, and Drs. Couture and DiGiusto, who direct the facility. The members of the program have initiated several novel therapeutics into the clinic and in the process have filed nearly a dozen INDs with the FDA for carry out their trials. The 11 Full and 10 Associate Members of the program have published 97 articles, books, book chapters, etc., since the last competitive grant review. Of these, 51 are intraprogrammatic publications, 12 are interprogrammatic publications, and 11 are both.